Molecular structure and vibrational and chemical shift assignments of 6-(2-hydroxyethyl)-2,3,4-triphenyl-2,6-dihydro-7H-pyrazolo[3,4-d] pyridazin-7-one by DFT and ab initio HF calculations

Article abstract of DOI:10.1016/j.molstruc.2010.11.002

The molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) ¹H and ¹³C chemical shift values and several thermodynamic parameters of 6-(2-hydroxyethyl)-2,3,4-triphenyl-2,6- dihydro-7H-pyrazolo[3,4-d]pyridaz

Full text of DOI:10.1016/j.molstruc.2010.11.002

Journal of Molecular Structure 985 (2011) 251–260
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Molecular structure and vibrational and chemical shift assignments
of 6-(2-hydroxyethyl)-2,3,4-triphenyl-2,6-dihydro-7H-pyrazolo-
[3,4-d]pyridazin-7-one by DFT and ab initio HF calculations
a
b
b
b
Sibel Demir a, , Muharrem Dinçer , Emine Sßahan , Elif Korkusuz , Ismail Yıldırım
⇑
_
a Department of Physics, Faculty of Arts and Sciences, Ondokuz Mayıs University, 55139 Kurupelit, Samsun, Turkey
b Department of Chemistry, Faculty of Arts and Sciences, Erciyes University, 38039 Kayseri, Turkey
a r t i c l e i n f o
a b s t r a c t
The molecular geometry, vibrational frequencies, gauge including atomic orbital (GIAO) 1H and 13C
chemical shift values and several thermodynamic parameters of 6-(2-hydroxyethyl)-2,3,4-triphenyl-
2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-7-one in the ground state have been calculated by using the
Hartree–Fock (HF) and density functional methods (B3LYP) with 6–31G(d) basis set. The results of the
optimised molecular structure are presented and compared with the experimental X-ray diffraction.
The calculated results show that the optimised geometries can well reproduce the crystal structural
parameters and the theoretical vibrational frequencies, and 1H and 13C NMR chemical shift values show
good agreement with experimental data. The computed vibrational frequencies are used to determine the
types of molecular motions associated with each of the experimental bands observed. To determine con-
formational flexibility, molecular energy profile of the title compound was obtained by semi-empirical
(AM1) with respect to selected degree of torsional freedom, which were varied from ꢀ180° to +180° in
steps of 10°. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMO), and ther-
modynamic properties were performed at HF and DFT levels of theory.
Article history:
Received 15 July 2010
Received in revised form 1 November 2010
Accepted 1 November 2010
Available online 6 November 2010
Keywords:
X-ray structure determination
B3LYP
Hartree–Fock
GIAO
1H and 13C NMR and vibrational assignment
AM1 semi-empirical method
Crown Copyright Ó 2010 Published by Elsevier B.V. All rights reserved.
1. Introduction
In this study, we present results of a detailed investigation of
the synthesis and structure characterization of 6-(2-hydroxy-
The title compound, is a derivative of 7H-pyrazolo[3,4-d]pyrida-
zin-7-one, which are reported as very important organic com-
pounds because they are widely used as pharmaceuticals and
agrochemicals. Their excellent control activities on various plant
diseases are studied [1,2]. Pyrazoles are important compounds that
have many derivatives with a wide range of interesting properties,
such as anti-hyperglycaemic, analgesic, antiinflammatory, anti-
pyretic, anti-bacterial, hypoglycaemic and sedative–hypnotic
activity. They were also reported to have non-nucleoside HIV-1
reverse transcriptase inhibitory activity [3,4]. Pyrazolo[3,4-d]pyr-
idazine derivative was obtained from cyclization of 4-benzoyl-
1,5-diphenyl-1H-pyrazole-3-carboxylic acid or -acid chloride with
2-hydroxyethyl hydrazine. The title compound is a novel com-
pound synthesized firstly in our laboratories by us. The possible
biological properties of the pyrazol, pyridazinone [5,6], and pyraz-
olo-pyridazinone [7,8] derivatives make it attractive to study these
compounds.
ethyl)-2,3,4-triphenyl-2,6-dihydro-7H-pyrazolo[3,4-d]pyridazin-
7-one using single crystal X-ray, IR, NMR and quantum chemical
methods, besides elemental analysis. The geometrical parame-
ters, fundamental frequencies and GIAO 1H and 13C NMR chemi-
cal shift values of the title compound in the ground state were
calculated using the Hartree–Fock (HF) and DFT (B3LYP) methods
with the 6–31G(d) basis set. These calculations are valuable for
providing insight into molecular parameters and the vibrational
and NMR spectra. The aim of this work is to explore the molecu-
lar dynamics and the structural parameters that govern the
chemical behaviour, and to compare predictions made from the-
ory with experimental observations.
2. Experimental
2.1. Synthesis
Melting points were measured on an Electrothermal 9200 appa-
ratus and are uncorrected. Microanalysis was performed using a
Leco-932 CHNS-O Elemental Analyzer. The 1H and 13C NMR spectra
were measured with a Bruker Avance III 400 MHz spectrometer
and the chemical shifts are expressed in ppm relatively to TMS.
⇑
Corresponding author. Tel.: +90 03623121919/5260; fax: +90 03624576081.
E-mail addresses: sibeld@omu.edu.tr, sibdemir@hotmail.com (S. Demir).
0022-2860/$ - see front matter Crown Copyright Ó 2010 Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2010.11.002

252
S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
literature procedure that described by Ziegler and co-workers [9]
and by Akçamur and co-workers [10,11]. The 4-benzoyl-1,5-diphe-
nyl-1H-pyrazole-3-carboxylic acid chloride (0.20 g, 0.52 mmol)
and 2-hydroxyethyl hydrazine (0.07 mL, 1.04 mmol) were refluxed
in xylene for 5 h. The solvent was evaporated, then the oily residue
was treated with diethyl ether and the formed crude product was
recrystallized from toluene. (Scheme 1) (yield: 0.16 g, 76%; m.p.
O
O
N
N
OH
O
Cl
N
N
H2NNH-CH2CH2OH
N
N
195 °C). IR (ATR,
m
, cmꢀ1): 3460 (OAH), 3065 (aromatic CAH),
2951, 2912 (aliph. CAH), 2000–1750 (overtone or combination
Scheme 1. Synthesis scheme of the title compound.
bands), 1662 (C@O), 1593–1446 (phenyl, pyridazine and pyrazole
rings C C, C N), 1225 (CAO). 1H NMR (400 MHz, CDCl3, d,
. . .
. . .
•
•
ppm): 7.43–6.85 (m, 15H, ArH), 4.58 (t, 2H, CH2AOH), 4.12
(t, 2H, NACH2), 2.73 (b, s, 1H, OH). 13C NMR (100 MHz, CDCl3, d,
ppm): 156.86 (C7@O), 144.46 (C7a), 142.65 (C4), 140.16 (C3)
138.89 (C9), 133.98, 130.43, 129.09, 128.99, 128.89, 128.66,
128.45, 128.16, 127.85, 127.74, 126.03 (arom. C’s), 116.68
(C3a), 62.41 (CH2AOH), 52.80 (NACH2). Analysis calculated for
When necessary to identify all C- and H-atoms, complementary
NMR experiments (HETCOR, and Exchange with D2O) were per-
formed. IR spectra of the compound were recorded in the range
of 400–4000 cmꢀ1 region with a Shimadzu FT-IR 8400 spectropho-
tometer. Solvents were dried by refluxing with the appropriate
drying agents and distilled before use. All other reagents were
purchased from Merck, Fluka, Aldrich and used without further
purification. The starting material was prepared according to the
C25H20N4O2 (408.45 g/mol): C 73.51, H 4.94, N 13.72%; found: C
73.25, H 4.73, N 13.89%.
Fig. 1. (a) The molecular structure of the title molecule, showing the atom-numbering scheme. Displacement ellipsoids are drawn at the %40 probability level and H atoms
are shown as small spheres of arbitrary radii. (b) The theoretical geometric structure of the title compound.

S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
253
Table 1
Table 2
Crystallographic data for title compound.
Hydrogen bonding geometry (Å, °) for the title compound.
Formula
C25 H20 N4 O2
408.45
296
0.71073
Triclinic
P-1
10.5875(7)
10.6820(7)
11.0305(7)
79.701(5)
69.871(5)
62.279(5)
1036.61(11)
2
1.309
428
ꢀ13 6 h 6 13
ꢀ13 6 k 6 13
ꢀ14 6 l 6 14
15,096
4765
0.0347
3567
0.0398
DAHꢁꢁꢁA
DAH
HꢁꢁꢁA
1.86(3)
2.92(2)
2.947(17)
DꢁꢁꢁA
2.7856(17)
3.736(2)
DAHꢁꢁꢁA
174(2)
141.8(14)
110.2(14)
Formula weight
Temperature (K)
Wavelength (Å)
Crystal system
Space group
a (Å)
O1AH1ꢁꢁꢁO2a
0.93(3)
0.969(19)
1.010(17)
C15AH15ꢁꢁꢁCg(2)
C18AH18ꢁꢁꢁCg(3)
3.430(16)
a
[ꢀx, 1 ꢀ y, 2 ꢀ z]; Cg(2): N3AC16; Cg(3): C4AC9.
b (Å)
c (Å)
a
(o)
3. Computational details
b (o)
c
(o)
V (Å3)
The molecular structure of the title compound in the ground state
(in vacuo) is optimised using Hartree–Fock (HF) and DFT(B3LYP)
[12,13] with the 6–31G(d) [14] basis set. For modeling, the initial
guess of the Scheme 1. Formation of the title compound was first
obtained from the X-ray coordinates. Then, vibrational frequencies
for the optimised molecular structures of the title compound were
calculated using these methods and then scaled by 0.8929 and
0.9613 [15], respectively. The geometry of the title compound,
together with that of tetramethylsilane (TMS), is fully optimised.
1H and 13C NMR chemical shifts were calculated within the GIAO
approach [16,17] applying the same methods and basis set as used
for geometry optimisation. The 1H and 13C NMR chemical shifts were
converted to the TMS scale by subtracting the calculated absolute
Z
Dcalc (g/cm3)
F(0 0 0)
h, k, l Range
Reflections collected
Independent reflections
Rint
Reflections observed [I P 2
r(I)]
R [I > 2
r
(I)]
(I)]
Rw [I > 2
r
0.1036
1.031
Shelxs-97
Full matrix
0.17, ꢀ0.13
Goodness-of-fit on Indicator
Structure determination
Refinement
(Dr)max, (Dr
min) (e/Å3)
chemical shielding of TMS (d = R0
is the absolute shielding and R0 is the absolute shielding of TMS),
ꢀR, where d is the chemical shift,
R
with values of 32.52 (1H) and 199.79 (13C) ppm for HF/6–31G(d) and
32.10 (1H) and 189.40 (13C) ppm for B3LYP/6–31G(d), respectively.
All calculations were performed using the GaussView Molecular
Visualization program [18] and Gaussian 03 program package [19]
on a personal computer without specifying any symmetry for the ti-
tle molecule. In order to describe conformational flexibility of the ti-
tle molecule, the selected torsion angle, T(N2AN1AC10AC11) and
T(C25AC24AN4AN3), was varied from ꢀ180 to 180° in every 10°
and the molecular energy profile as a function of the selected
torsional degree of freedom is obtained by performing single point
2.1.1. Crystal data for the title compound
CCDC 770493, C25 H20 N4 O2, triclinic, space0 group Pꢀ1; Z = 2,
a = 10.5875(7), b = 10.682(7), c = 11.0305(7) ÅA,
a = 79.701(5),
b = 69.871(5),
c
= 62.279(5)°; V = 1036.61(11) Å3, F(0 0 0) = 428,
Dx = 1.309 g cmꢀ3
.
Full crystallographic data are available as supplementary
material.
Fig. 2. Part of the crystal structure of the title molecule, showing the formation of a chain of centrosymmetric R dimers. For the charity, only H atoms involved in hydrogen
bonding have been included.

254
S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
Fig. 3. FT-IR (ATR) spectrum of the title compound.
For the calculations of the MEP [20,21], the same level of theory
B3LYP/6–31G(d), were used. The thermodynamic properties of the
title compound at different temperatures were calculated on the ba-
sis of vibrational analyses, using B3LYP/6–31G(d) level.
Table 3
Comparison of the observed and calculated vibrational spectra of the title compound.
Assignments
Experimental IR Calculated (cmꢀ1
)
with ATR (cmꢀ1
)
(6–31(d))
HF
DFT/B3LYP
4. Results and discussion
m
OAH (hydroxy ethyl)
3460
–
3642
3042–
3030
3026–
3016
2971
2925–
2837
1728
1647
1620–
1588
1562
3389
3123–
3106
3103–
3090
3038
2979–
2891
1615
1474
1599–
1570
1534
ms CAH (phenyl ring)
4.1. Crystal structure
mas CAH (phenyl ring)
3065
The title compound, an Ortep-3 [22] view of which is shown in
Fig. 1, crystallises in the triclinic space group P-1 with two
molecules in the unit cell, details of which are given in Table 1.
The asymmetric unit in the crystal structure contains only one
molecule. The title molecule is composed of a hydroxylethyl,
triphenyl and dihydropyrazolo pyridazine group.
There are two obviously different CAN bond distances in the
pyrazole ring, viz. C1@N2 and C3AN1. The C1@N2 bond length is
all longer than and C3AN1 bond length is all shorter than those
found in similar structures [C@N 1.291(2) ꢀ 1.300(10) Å, CAN
1.482(2) ꢀ 1.515(9) Å] [23], resulting from the conjugation of elec-
trons of atom N with atom C. In this relation, these results are con-
sistent with the respect to the different pyrazole derivatives.
Moreover, the NAN bond length (1.356 Å) is shorter than those
found in the above-cited structures [NAN 1.373(2) ꢀ 1.380(8) Å]
[24]. In the title compound, six atoms of pyridine ring defines a
plane (P). The P is nearly orthogonal to plane the consist of C24,
C25 and O1 atoms, with the dihedral angle between them being
80.18 (7)°.
mas CH2 (hydroxy ethyl)
ms CH2 (hydroxy ethyl)
2951
2912
m
m
m
C@O + bCACAN
C@N (pyridazin)
CAC (phenyl ring)
1662
1593
–
m
a
C@C +
m
C@N (pyrazol)
1446
CH2
–
–
–
1492/1453 1502
1493
1468
bCAH (phenyl ring)
1500
1495
c
c
m
CAH +
(pyrazol)
OAH + CH2
aCH2 + m CACAC
x
–
1423–
1373
1364
1401–
1375
1345
CANAC +
m
CANAN (pyrazol)
–
–
–
dCH2
CH2
1342/1247 1355
c
1307–
1282
1230
1214
1192–
1158
1345–
1338
1327
–
1192–
1176
bCANAN (pyrazol + pyridin)
m
a
–
–
–
NAN (pyrazol ring)
CAH
m
CAO +
c
CH2
1225
1110/1041 1107
Perspective view of the crystal packing in the unit cell is shown
in Fig. 2. In the crystal structure, intermolecular OAHꢁꢁꢁO hydrogen
bonds form centrosymmetric dimers which are linked by further
OAHꢁꢁꢁO hydrogen bonds involving hydroxyethyl molecules
(Fig. 2). Hydroxyl atom in the ethyl at (x, y, z) acts as hydrogenA
bond donor, via atom H1, to ring atom O2 in the molecule at
(ꢀx, 1 ꢀ y, 2 ꢀ z), so generating by inversion a centrosymmetric
dimer characterized by R22 (14) motif [25] (Fig. 2). There is two
d CAH
–
–
–
–
1098–984 997/965
H
H
(phenyl ring)
(pyrazol ring)
973
958
835
808
958
958
941
806
m
CAC (hydroxy ethyl)
b deformation
(pyrazol + pyridin)
782–740
x
c
(phenyl ring)
OAH
708–650
–
805–689
370
804–701
495
Notes: Vibrational modes:
m, stretching; s, symmetric; as, asymmetric; a, scissoring;
CAHꢁꢁꢁCg (
of which are given in Table 2. Atom C15 at (x, y, z) forms a CAHꢁꢁꢁCg
-ring) contact, via atom H15, with the centroid of the N3AC16
p-ring) (edge to face) intermolecular interactions, details
c
, rocking; , wagging; d, twisting; h, ring breathing; b, in-plane bending.
x
(p
calculations on the calculated potential energy surface, and the
molecular energy profile was obtained at the AM1 computations.
ring [fractional centroid coordinates: 0.3791(5), 0.31887(5),
0.71339(5)] of the molecular at (1 ꢀ x, 1 ꢀ y, 1 ꢀ z). In addition,

S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
255
Fig. 4. Correlation graphics of calculated and experimental frequencies of the title compound.
Table 4
dinates: 0.66406(7) 0.15893(7) 0.22876(6)] of the molecula at
(x, y, z) (Fig. 2). Additional information for the structure determina-
tions are given in Table 2.
Theorical and experimental 13C and 1H isotropic chemical shifts (with respect to TMS
all values in ppm) for the title compound.
Atom
Experimental (CDCl3)
Calculated chemical shift (ppm)
4.2. Vibrational spectra
B3LYP
HF
C1
C2
C3
C4
C5
C6
C7
C8
144.46
116.28
142.65
128.99
127.74
128.66
128.89
128.66
126.03
140.16
126.68
129.09
130.43
–
136.83
109.5
129.85
123.36
118.87
111.68
110.83
113.82
119.22
132.74
112.82
114.45
111.92
112.64
111.6
137.26
126.56
116.6
109.25
107.13
111.75
114.78
144.67
37.69
47.66
1.75
5.47
4.96
5.19
5.45
5.61
5.57
5.89
5.6
5.56
4.67
4.87
4.89
5
4.47
5.53
0.945
1.44
146.79
109.71
144.42
125.01
126.69
117.83
120.35
120.18
126.86
135.52
119.59
120.49
119.74
118.65
118.79
151.16
128.78
124.08
114.9
115.33
118.08
122.71
158.38
35.4
43.8
0.39
5.93
5.25
5.66
6.12
6.08
5.95
6.31
6.04
5.94
5.01
5.16
5.18
5.46
5.05
The FT-IR (ATR) spectrum of the title compound is shown in
Fig. 3. The vibrational bands assignments have been made by using
Gauss- View molecular visualization program [18]. Table
3
presents the calculated vibrational frequencies and their experi-
mentally measured values. We have compared our calculation of
the title compound with their experimental results. To make
comparison with experiment, we present correlation graphics in
Fig. 4 based on the calculations. As we can seen from calculation
graphic in Fig. 4 experimental fundamentals are in better agree-
ment with scaleted Fundamentals and are found to have a better
correlation for HF than B3LYP. The frequency calculations were
carried out at the same level as the respective optimisation process
and by analytic evaluation of second derivatives of energy with
respect to the nuclear displacement.
C9
C10
C11
C12
C13
C14
C15
C16
C17
C18
C19
C20
C21
C22
C23
C24
C25
H1
126.68
138.89
–
128.16
128.45
133.98
128.45
127.85
156.86
52.86
62.41
2.73
7.38
7.12
6.82
7.10
7.36
7.23
7.04
6.83
7.03
7.22
7.30
7.18
It is well known, that the calculated HF and DFT ‘raw’ or
‘non-scale’ harmonic frequencies could significantly overestimate
experimental values due to lack of electron correlation, insufficient
basis sets and anharmonicity.
Most bands observed in infrared spectra of the title compound
belong to modes of 6-(2-hydroxyethyl)-2,3,4-triphenyl-2,6-dihy-
dro-7H-pyrazolo[3,4-d]pyridazin-7-one substituents only some of
them may be assigned to group ring CAH and C@C/CAC stretching.
These bands have been calculated at 3042–3030 (CAH asymmet-
ric), 3026–3016 (CAH symmetric) and 1620–1588 cmꢀ1 (C@C/
CAC stretching) for HF level, and 3123–3106, 3103–3090 and
1599–1570 cmꢀ1 for B3LYP level. In the pyrazolo ring, the
C@N + C@C and CANAC + CANAN stretching are found to be
1562, 1364 cmꢀ1 for HF/6–31G(d) level and 1534, 1345 cmꢀ1 for
B3LYP/6–31G(d) level.
Other essential characteristic vibrations of the title compound
are C@N (pyridazine ring) and OAH stretching. These modes have
been calculated at 1647, 3642 cmꢀ1 with HF/6–31G(d) and 1474,
3389 cmꢀ1 with B3LYP/6–31G(d) , these result from different sub-
stitute atoms or atom groups in the molecular structure. The other
modes can also be seen in Table 3.
H5
H6
H7
H8
H9
H11
H12
H13
H14
H15
H18
H19
H20
H21
H22
H24a
H25a
7.13
7.20
7.32
4.12
5.97
0.795
1.23
4.58
a
Average.
4.3. NMR spectra
atom C18 at (x, y, z) forms a CAHꢁꢁꢁCg (
p
-ring) contact, via atom
GIAO 1H and 13C NMR chemical shift calculations were carried
out using the HF and B3LYP methods with the 6–31G(d) basis set
H18, with the centroid of the C4AC9 ring [fractional centroid coor-

256
S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
for the optimised geometry. The theoretical GIAO 13C and 1H chem-
ical shift values (with respect to TMS) of the title compound are
generally compared to the experimental 13C and 1H chemical shift
values. The results of these calculations are also shown in Table 4.
The 1H NMR chemical shift values (with respect to TMS) have
been calculated to be 0.39–6.31 ppm with HF level and 0.945–
5.89 ppm with B3LYP level, whereas the experimental results are
observed to be 7.38–2.73 ppm. Since experimental 1H chemical
shift values were not available for individual hydrogen, we present
the average values for CH2 hydrogen atoms. The two triplet ob-
served at 4.12 and 4.18 ppm are belonged to H24ꢂ (C24), H25ꢂ
(C25) atoms that have been calculated at 0.795 (H24ꢂ) and 1.23
(H25ꢂ) ppm for HF levels, 0.945 (H24ꢂ) and 1.44 (H25ꢂ) ppm for
B3LYP levels. The AOHA signals of the hydroxyethyl are observed
at 2.73 ppm. The CAH signals of phenyl adjacent to the 7H-pyraz-
olo[3,4-d]pyridazine are observed at 6.82–7.38, 6.83–7.23, and
7.13–7.32 ppm.
ing value in optimised geometries is 166.180° and ꢀ84.401° for HF/
6–31G(d) and 167.396° and ꢀ92.380° for B3LYP/6–31G(d).
Molecular energy profiles with respect to rotations about the
selected torsion angles are presented in Fig. 6. According to the re-
sults, the low energy domains for T(N2AN1AC10AC11) are located
at ꢀ130°, ꢀ50°, 40° and 130° having energy of 2.03377, 2.03323,
2.03396 and 2.03302 a.u., respectively, while they are located at
ꢀ70° and 80° having energy of 0.20562 and 0.20512 a.u., respec-
tively, for T(C25AC24A N4AN3). The energy difference between
the most favourable and most unfavourable conformers, which
arises from the rotational potential barrier calculated with respect
to the selected torsion angle is calculated as 0.03766 a.u. for
T(N2AN1AC10AC11) and as 0.00127 a.u. for T(C25AC24A
Table 5
Selected optimised and experimental geometries parameters of the title compound in
ground state.
13C NMR chemical shift values (with respect to TMS) are ob-
served to be 156.86–52.86 ppm range and found to be 158.38–
35.4 ppm range by HF level and 144.67–37.69 ppm range by
B3LYP. The chemical shift value of C23 atom bounded pyridazine
ring are observed as 156.86 ppm, whereas the corresponding val-
ues are 144.67 ppm for B3LYP level and 158.38 ppm for HF level.
While the two aliphatic CH2 (C24 and C25) carbons of belonging
to the hydroxyethyl group are observed at 52.86 and 62.41 ppm,
respectively. The other calculated chemical shift values can be seen
in Table 4.
Parameters
Experimental
Calculated
HF 6–31G(d)
DFT/B3LYP
6–31G(d)
Bond lengths (Å)
C(25)AO(1)
C(24)AN(4)
C(25)AC(24)
N(4)AC(23)
C(23)AC(1)
C(1)AC(2)
C(2)AC(16)
C(16)AN(3)
C(16)AC(17)
C(17)AC(22)
C(22)AC(21)
C(21)AC(20)
C(20)AC(19)
C(19)AC(18)
C(18)AC(17)
C(1)AN(2)
N(2)AN(1)
N(1)AC(3)
C(3)AC(2)
C(3)AC(4)
C(4)AC(9)
C(9)AC(8)
C(8)AC(7)
C(7)AC(6)
C(6)AC(5)
1.402(4)
1.467(3)
1.472(4)
1.343(4)
1.347(3)
1.376(4)
1.375(4)
1.404(4)
1.501(4)
1.479(4)
1.388(4)
1.383(5)
1.367(5)
1.376(5)
1.366(5)
1.394(4)
1.224(3)
1.464(4)
1.381(5)
1.392(6)
1.392(7)
1.332(7)
1.367(6)
1.385(5)
1.441(4)
1.383(4)
1.372(4)
1.383(5)
1.389(4)
1.379(4)
1.372(4)
1.370(3)
1.427(5)
1.308
1.194
1.483
1.300
1.323
1.360
1.370
1.415
1.500
1.496
1.388
1.386
1.383
1.388
1.381
1.392
1.196
1.484
1.392
1.382
1.386
1.384
1.386
1.390
1.426
1.390
1.375
1.394
1.385
1.389
1.377
1.345
1.400
0.0681
0.273
1.446
1.476
1.531
1.398
1.448
1.428
1.446
1.321
1.485
1.407
1.397
1.400
1.399
1.398
1.406
1.341
1.377
1.388
1.408
1.476
1.408
1.397
1.400
1.400
1.398
1.407
1.436
1.401
1.397
1.400
1.400
1.398
1.400
0.0685
0.153
4.4. Theoretical structures
Selected geometric parameters obtained experimentally and
those calculated theoretically using HF and B3LYP with the 6–
31G(d) basis set are listed in Table 5. It is well known that DFT
optimised bond lengths are usually longer and more accurate than
HF, due to the inclusion of electron correlation. However, according
to our calculations, the HF method correlates well for the bond
length compared with B3LYP method (Table 5). Although the larg-
est difference between experimental and calculated bond lengths
is about 0.273 Å for HF and 0.153 Å for B3LYP. The root mean
0
square error (RMSE) is found to be about 0.0681 ÅA for HF and
0
0.0685 ÅA for B3LYP, indicating that the bond lengths obtained by
the HF method show the strongest correlation with the experimen-
tal values.
When the X-ray structure of the title compound is compared
with its optimised counterparts (see Fig. 5), conformational
discrepancies are observed between them.
A logical method for globally comparing the structures obtained
with the theoretical calculations is by superimposing the
molecular skeleton with that obtained from X-ray diffraction,
giving a RMSE of 0.174 Å for HF/6–31G(d) and 0.240 Å for B3LYP/
6–31G(d) calculations (Fig. 5). Consequently, the HF method
correlates well for the geometrical parameters when compared
with B3LYP.
C(5)AC(4)
N(1)AC(10)
C(10)AC(11)
C(11)AC(12)
C(12)AC(13)
C(13)AC(14)
C(14)AC(15)
C(15)AC(10)
RMSEa
Max. differencea
Bond angles (°)
O(1)AC(25)AC(24)
O(2)AC(3)AC(1)
N(2)AN(1)AC(10)
N(1)AC(3)AC(4)
N(3)AC(16)AC(17)
N(3)AN(4)AC(24)
C(2)AC(16)AC(17)
C(3)AC(2)AC(16)
C(10)AN(1)AN(3)
RMSEa
112.5(2)
106.1(2)
105.2(2)
111.8(2)
120.9(3)
119.5(2)
127.9(2)
119.7(3)
112.5(2)
112.237
106.132
104.196
111.377
122.193
118.465
129.256
119.803
114.150
0.975
113.786
126.586
117.221
122.958
114.667
114.455
125.450
136.799
129.457
12.204
4.5. Conformational analysis
Based on HF/6–31G(d) and B3LYP/6–31G(d) optimised geome-
try, the total energy of the title compound has been calculated by
these two methods, which are ꢀ1325.84085901 and ꢀ1333.762
62692 a.u., respectively. In order to define the preferential position
of 7H-pyrazolo[3,4-d]pyridazine system with respect to the 6–2-
hydroxyethyl and phenyl ring, a preliminary search of low-energy
structures was performed using AM1 computation as a function of
the selected torsion angle T(N2AN1AC10AC11) and T(C25AC24A
N4AN3). The respective value of the selected torsion angles are
165.4 (3) and ꢀ72.1° in the X-ray structure, whereas the correspond-
Max. differencea
1.65
20.486
Torsiyon angles (°)
C(11)AC(10)AN(2)AN(1)
N(2)AC(1)AC(23)AN(4)
165.4(3)
118.1(4)
166.180
113.543
167.396
118.756
a
RMSE and maximum differences between the bond lengths and angles com-
puted using theoretical methods and those obtained from X-ray diffraction.

S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
257
Fig. 5. Atom-by-atom superimposition of the structures calculated (black) (A = HF/6–31G(d), B = B3LYP/6–31G(d)) on the X-ray structure (red) of the title compound
hydrogen atoms have been omitted for clarity. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
2,075
2,070
2,065
2,060
2,055
2,050
2,045
2,040
2,035
2,030
-200
-150
-100
-50
0
50
100
150
200
T (N2-N1-C10-C11)
0,218
0,216
0,214
0,212
0,210
0,208
0,206
0,204
-200
-150
-100
-50
0
50
100
150
200
T (C25-C24-N4-N3)
Fig. 6. Molecular energy profile of the optimised counterpart of the title compound versus selected degrees of torsional freedom.

258
S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
N4AN3), when both selected degrees of torsional freedom are
considered.
The molecular energy can be divided into bonded and non-
bonded contributions. The bonded energy is considered to be inde-
pendent of torsional angle changes and therefore vanished when
relative conformer energies are calculated. The non-bonded energy
is further separated into torsional steric and electrostatic terms
[18]. Since the title compound contains no intramolecular hydro-
gen bond, it can be deduced from the computational results that
the most stable conformer of the title compound is principally
determined by the non-bonded torsional energy term affected by
packing of the molecules.
Fig. 7. Molecular electrostatic potential map calculated at B3LYP/6–31G(d) level.
Fig. 8. Molecular orbital surfaces and energy levels given in parentheses for the HOMO-1, HOMO, LUMO and LUMO + 1 of the title compound computed at B3LYP/6–31G(d)
level.

S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
259
Table 6
4.6. Molecular electrostatic potential
Calculated energies (a.u.), zero-point vibrational energies (kcal molꢀ1), rotational
constants (GHz), entropies (cal molꢀ1 Kꢀ1
compound.
) and dipole moment (D) of the title
The molecular electrostatic potential, V(r), at a given point r
(x, y, z) in the vicinity of a molecule, is defined in terms of the inter-
action energy between the electrical charge generated from the
molecule electrons and nuclei and a positive test charge (a proton)
located at r. For the system studied, the V(r) values were calculated
as described previously using the equation [26]:
Parameters
HF 6–31G(d)
B3LYP 6–31G(d)
Dipole moment (D)
7.888
8.8258
255.17343
Zero-point vibrational
272.50275
energy kcal molꢀ1
Total energy (a.u.)
Rotational constants
)
ꢀ1325.84085
0.18130
ꢀ1333.76262
0.17630
Z
X
VðrÞ ¼
ZA=jRA ꢀ rj ꢀ
q
ðr0Þ=jr0 ꢀ rjd3r0
0.13279
0.08312
0.13022
0.08012
where ZA is the charge of nucleus A located at RA,
q
(r0) is the elec-
Entropy (cal molꢀ1 Kꢀ1
Rotational
Translational
Vibrational
)
tronic density function of the molecule, and r0 is the dummy inte-
gration variable.
36.328
43.911
87.225
167.463
36.412
43.911
92.409
172.731
The molecular electrostatic potential (MEP) is related to the
electronic density and is a very useful descriptor for determining
sites for electrophilic attack and nucleophilic reactions as well as
hydrogen-bonding interactions [27,28]. The electrostatic potential
V(r) is also well suited for analysing processes based on the ‘recog-
nition’ of one molecule by another, as in drug–receptor and en-
zyme–substrate interactions, because it is through their
potentials that the two species first ‘see’ each other [29,30]. Being
a real physical property, V(r) can be determined experimentally by
diffraction or by computational methods [31].
Total
Table 7
Thermodynamic properties of the title compound at different temperatures at the
B3LYP/6–31G(d) level.
Cp0;m (cal molꢀ1 Kꢀ1
)
S0m (cal molꢀ1 Kꢀ1
)
D )
H0m (kcal molꢀ1
T (K)
100.00
200.00
298.15
300.00
400.00
500.00
600.00
700.00
800.00
36.468
53.152
96.145
98.273
109.867
172.731
173.123
165.285
191.923
269.171
298.094
325.220
2.237
5.395
To predict reactive sites for electrophilic and nucleophilic attack
for the title molecule, MEP was calculated at the B3LYP/6–31G(d)
15.290
15.624
21.367
32.880
46.166
74.967
94.512
98.140
optimised geometry. The negative (red1
) regions of MEP were re-
107.002
127.750
176.984
194.124
208.029
lated to electrophilic reactivity and the positive (blue) regions to
nucleophilic reactivity shown in Fig. 7. As easily can be seen in
Fig. 7 this molecule has two possible sites for electrophilic attack.
The negative regions are mainly over the O1 and O2 atoms. For
the title compound, negative regions were calculated: the MEP
value around O2 is more negative than that of O1. These results
provide information concerning the region where the compound
can interact intermolecularly and metallic bonding. Therefore,
Fig. 7 confirms the existence of an intermolecular OAHꢁꢁꢁO interac-
tion between the protonated and unprotonated O atoms of the
hydroxy ethyl and pyridazine.
cal thermodynamic functions i, Standard heat capacities (C0p;m),
standard entropies (S0m), and standard enthalpy changes ( Hm0
D
(0 ? T)) were obtained and are listed in Table 7. The scale factor
for the frequencies is 0.9613, which is a typical value for the
B3LYP/6–31G(d) level of calculations. As can be seen from Table
7, the standard heat capacities, entropies and enthalpy changes in-
crease at any temperature from 100.00 to 800.00 K, since increas-
ing the temperature causes an increase in the intensity of the
molecular vibration.
4.7. Frontier molecular orbitals analysis
The frontier molecular orbitals play an important role in the
electric and optical properties, as well as in UV–Vis spectra and
chemical reactions [32]. Fig. 8 shows the distributions and energy
levels of the HOMO–1, HOMO, LUMO and LUMO + 1 orbitals com-
puted at the B3LYP/6–31G(d) level for the title compound. As can
be seen from the figure, both the highest occupied molecular
orbital (HOMO) and the lowest-lying unoccupied molecular orbital
(LUMO) are mainly delocalised among all the atoms. Both the
highest occupied molecular orbitals (HOMOs) and the lowest-lying
unoccupied molecular orbitals (LUMOs) are mainly located at the
For the title compound, the correlation equations between
these thermodynamic properties and temperature T, which can
be used for further studies of the title compound, are as follows:
C0p;m ¼ 15:995 þ 0:2276T þ 1:5742T2ðR2 ¼ 0; 9634Þ
S0m ¼ 91:09 þ 0:128T þ 2:03003 ꢃ 10ꢀ4T2ðR2 ¼ 0; 96119Þ
H0m ¼ 4:83033 ꢀ 0:02696T þ 1:73829 ꢃ 10ꢀ4T2ðR2 ¼ 0; 9889Þ
rings and mostly the
p-antibonding type orbitals. The value of
the energy separation between the HOMO and LUMO is 4.204 eV
and this energy gap indicates that the title structure is very stable.
5. Conclusions
4.8. Thermodynamic properties
In this study, we have synthesized a novel compound 7H-pyraz-
olo[3,4-d]pyridazin-7-one derivative, C25H20N4O2, and character-
ized by spectroscopic (FT-IR, NMR) and structural (XRD)
techniques as well as microanalysis. To fit the theoretical frequency
results with experimental ones for HF and B3LYP levels, we have
multiplied the data. Multiplication factors results gained seemed
to be in a good agreement with experimental ones. The X-ray struc-
ture is found to be very slightly different from its optimised counter-
parts, and the crystal structure is stabilised by a CAHꢁꢁꢁO and
OAHꢁꢁꢁO type hydrogen bonds. The results of the HF method show
a better fit to experimental values than B3LYP in evaluating
Several thermodynamic parameters have been calculated using
HF and B3LYP with 6–31G(d) basis set. Table 6 demonstrates ther-
modynamic parameters of the title compound without of results of
experimental.
Besides, based on the vibrational analysis at the B3LYP/6–
31G(d) level and statistical thermodynamics, the standard statisti-
1
For interpretation of color in Fig. 7, the reader is referred to the web version of
this article.

260
S. Demir et al. / Journal of Molecular Structure 985 (2011) 251–260
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Acknowledgement
This study was supported financially by the Research Centre of
Ondokuz Mayıs University (Project No: F-461).
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